The overall objective is the application of a new methodology currently bieng developed in the investigator's laboratory, to the total synthesis of steroids, 19-norsteroids, C-nor-D-homosteroids, and aphidicolin. The work will utilize an organoiron complex as the ring A precursor for the target molecules, in a new reaction which joins three of the steroid rings (two of aphidicolin) in one step. The new methodology has considerable potential flexibility and can be used for synthesis of analogues of the natural molecules, an may also be used for synthesis of specifically radiolabelled, or carbon-13- or deuterium-labelled compounds, thereby providing compounds for use for both in vitro and in vivo studies of mode of action and metabolism, a particularly desirable feature for the steroid synthesis. The total synthesis of steroids is becoming an increasingly important area of chemical research, these compounds being used extensively in medicine both in birth control, as antiinflammatory drugs (corticosteroids) and in veterinary medicine. Total synthesis is important because it gives a means of producing analogues which retain the medicinal value but do not have the unpleasant side effects of many of the substances found in nature. The C-nor-D-omosteroid ring system is present in veratrum alkaloids and our long-term objective is the preparation of these compounds, which are used medicinally as antihypertensive agents. We anticipate developing synthesis of analogues which reatin the antihypertensive activity but which show reduced emetic side effects. Aphidicolin is a recently isolated antiviral agent, and is therefore an important synthetic objective. Modifications of this molecule, and the subsequent effect on its antiviral properties, have not been studied, and total synthesis offers the possibility of achieving this. Total synthesis of these substances is also important for two further reasons: (1) Some of the medicinally valuable compounds are isolated from natural sources only in small amounts. (2) The natural sources are often found in geographically remote or politically unstable areas, which would lead to loss of availability in the event of crisis.